Brief report

A double blind, placebo-controlled trial of demeclocycline treatment of polydipsia-hyponatremia in chronically psychotic patients

Polydipsia is defined at the intake of excessive fluid (>3 L daily). Psychogenic polydipsia (PPD) presents without an identifiable medical cause and is often seen in patients with diagnoses of schizophrenia, OCD, anxiety, alcohol use disorder, and other psychotic disorders. The purpose of this systematic review is to assess the therapeutic effect of various non-antipsychotic medications on patients with a stable psychotic illness and concurrent PPD.

A systematic search was conducted using the following databases: PubMed, MEDLINE with Full Text, CINAHL complete, Cochrane database of systematic reviews, Cochrane methodology register, MasterFILE Premier, APA PsychArticles, APA PsychInfo, APA PsycBooks, APA PsycTests, TRIP, Nursing and Allied Health. The quality of each retained study was assessed using appropriate risk of bias tools based on study design.

The initial search resulted in 1422 articles from which 22 articles were included for qualitative synthesis. Study designs ranged from case reports to double blind, placebo controlled randomized trials and was interpreted uniquely based on study design. Acetazolamide was effective in improving some PPD outcomes. Fluoxetine at high doses was effective in reducing fluid intake and polydipsia. Other medications included in this review performed equivocally for reduction of numerous parameters evaluating PPD.

No one drug appeared to be the most efficacious; however, some did show promise in specific populations. Those in need of pharmacotherapeutic options for PPD may consider one of the included agents to assist with co-morbid state. Further high-quality research is needed to provide better treatment guidance for PPD.

Several lines of studies have shown the existence of an important inhibitory mechanism for the control of water intake involving adrenergic α2A receptors (ADRA2A). A human study using patients with schizophrenia demonstrated an exacerbation of polydipsia by the administration of clonidine, an ADRA2A-agonist, and a relief of polydipsia by mianserin, an ADRA2A-antagonist, suggesting the involvement of the central adrenergic system in the drinking behavior of patients with schizophrenia. Based on these findings we examined a possible association between the C-1291G polymorphism in the promoter region of the ADRA2A gene and polydipsia in schizophrenia using a Japanese case-control sample. Our sample includes 348 patients with schizophrenia (DSM-IV) (84 with polydipsia and 264 without polydipsia). No significant association between the ADRA2A C-1291G polymorphism and polydipsia was found. Our result suggests that the ADRA2A C-1291G polymorphism may not confer susceptibility to polydipsia in schizophrenia in our sample. Further studies with larger samples are warranted.

A pilot study was conducted in schizophrenic patients with primary polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and primary polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 μg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and primary polydipsia provide little overall support for the effectiveness of clonidine treatment in primary polydipsia associated with schizophrenia.

Polydipsia occurs frequently in chronic schizophrenic patients, some of whom develop intermittent hyponatremia. Most therapeutic efforts have tried to control the hyponatremia. Four schizophrenic patients, followed for more than one year, showed improvement on clozapine. Case 1 was an outpatient without history of hyponatremia who improved from polydipsia and psychosis. The last three were inpatients with polydipsia, intermittent hyponatremia, and psychosis who showed minimal improvement of psychosis but significant decrease in polydipsia and water intoxication. Case 2 relapsed to polydipsia when clozapine was discontinued on two occasions. Case 3 demonstrated polyuria during 39% of days before clozapine and in 0% of days after two weeks of clozapine. In case 4, most baseline sodium levels were abnormal, but all became normal after clozapine. A time-series analysis for intervention effects showed a significant effect of clozapine (p=.017). The limited information provided by these case reports suggest the need for controlled studies of the clozapine effect on polydipsic patients.

La hiponatremia es el trastorno electrolítico más prevalente en las Unidades de Cuidados Intensivos. Se asocia a un aumento de la morbilidad, mortalidad y estancia hospitalaria. La mayoría de los estudios publicados hasta el momento son observacionales, retrospectivos y no incluyen pacientes críticos, lo que dificulta la extracción de conclusiones sólidas. Además, debido a la escasa evidencia científica de calidad, incluso las recomendaciones realizadas por distintas sociedades científicas recientemente publicadas difieren en aspectos importantes como son el diagnóstico o el tratamiento de la hiponatremia.

Los mecanismos etiopatogénicos en los pacientes críticos suelen ser complejos. Sin embargo, hay que profundizar en ellos para llegar al diagnóstico más probable y a la pauta de tratamiento más adecuada. Todo ello, ha motivado la realización de esta revisión práctica sobre aspectos útiles en el abordaje de la hiponatremia en las Unidades de Cuidados intensivos, con el objetivo de homogeneizar el manejo de esta entidad y disponer de un algoritmo diagnóstico a nivel nacional.

Hyponatremia is the most prevalent electrolyte disorder in Intensive Care Units. It is associated with an increase in morbidity, mortality and hospital stay. The majority of the published studies are observational, retrospective and do not include critical patients; hence it is difficult to draw definitive conclusions.

Moreover, the lack of clinical evidence has led to important dissimilarities in the recommendations coming from different scientific societies.

Finally, etiopathogenic mechanisms leading to hyponatremia in the critical care patient are complex and often combined, and an intensive analysis is clearly needed. A study was therefore made to review all clinical aspects about hyponatremia management in the critical care setting. The aim was to develop a Spanish nationwide algorithm to standardize hyponatremia diagnosis and treatment in the critical care patient.